{"entity":{"id":"urothelial-cancer","kind":"indication","name":"Urothelial cancer","aka":["bladder cancer","transitional cell carcinoma","urothelial carcinoma","UC"],"tldr":"Urothelial cancer mostly starts in the bladder lining and ranges from tumours that stay superficial and are managed for years with local treatments to disease that spreads and needs systemic therapy. Survival depends heavily on how early it is caught, which is why so much attention goes into staging it accurately.","summary":"Urothelial cancer, most commonly bladder cancer, arises from the transitional epithelium lining the urinary tract. GLOBOCAN 2022 estimated 614,298 new cases and 220,596 deaths worldwide, with roughly 75% of the burden occurring in men, while the newer GLOBOCAN 2024 release put incidence at 635,264 cases, ranked eighth worldwide, and mortality at 227,626 deaths, ranked thirteenth. In the United States, SEER projects 84,530 new cases and 17,870 deaths for 2026, with an incidence rate of 17.9 per 100,000 and a death rate of 4.1 per 100,000. Five-year relative survival is 79.1% overall, but this conceals a very wide stage gradient: 98.0% for in situ disease, which makes up half of cases, 73.0% for localised disease, 41.8% for regional disease, and only 9.6% for distant disease.\n\nTreatment is stratified by depth of invasion and risk. Non-muscle-invasive disease is treated with transurethral resection followed by intravesical chemotherapy and, for higher-risk tumours, bacillus Calmette-Guerin; BCG-unresponsive disease now has three FDA-approved options, pembrolizumab, the intravesical gene therapy nadofaragene firadenovec, and radical cystectomy for those fit for surgery. Muscle-invasive disease is treated with neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy, or with bladder-sparing trimodal chemoradiation, and since 2025 with perioperative pembrolizumab plus enfortumab vedotin, an approval extended in 2026 to cisplatin-eligible patients based on KEYNOTE-B15/EV-304. Adjuvant nivolumab is standard after cystectomy in patients at high recurrence risk. Metastatic disease is now led by enfortumab vedotin, an antibody-drug conjugate targeting Nectin-4, combined with pembrolizumab as first-line therapy regardless of cisplatin eligibility, with erdafitinib reserved for the roughly 20% of patients whose tumours carry an actionable FGFR2/3 alteration.\n\nNuclear medicine's role in staging urothelial cancer remains unsettled and is limited chiefly by physiology. FDG accumulates in urine and is excreted through the collecting system, obscuring the primary tumour and adjacent pelvic nodes on FDG PET/CT, the exact anatomical region that matters most for surgical planning. AUA, EAU, ESMO and NCCN guidelines diverge as a result: the US-oriented consensus is to avoid routine PET in initial staging and consider it only in selected or indeterminate cases, while ESMO and EAU jointly recommend systematic FDG PET/CT staging in oligometastatic patients being considered for radical treatment, to avoid overtreatment. Meta-analysis nodal-staging accuracy is modest across all modalities, with pooled sensitivity of about 0.40 for CT, 0.60 for MRI and 0.56 for FDG PET/CT against specificities around 0.91 to 0.92, leaving occult nodal disease a persistent blind spot before radical cystectomy.","asOf":"2026-09-23","links":[{"label":"IARC GLOBOCAN 2024 bladder factsheet","url":"https://gco.iarc.who.int/media/globocan/factsheets/cancers/30-bladder-fact-sheet.pdf"},{"label":"SEER Cancer Stat Facts: bladder cancer","url":"https://seer.cancer.gov/statfacts/html/urinb.html"},{"label":"NCI PDQ: bladder cancer treatment, health professional version","url":"https://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq"},{"label":"FDA approval: enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer","url":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-enfortumab-vedotin-ejfv-pembrolizumab-locally-advanced-or-metastatic-urothelial-cancer"},{"label":"Guideline of guidelines: muscle-invasive bladder cancer, PMC","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8057355/"},{"label":"PET imaging in bladder cancer: an update and future direction, MDPI","url":"https://www.mdpi.com/1424-8247/16/4/606"}],"tags":["urological","staging","nodal-staging"],"related":["nectin4","fdg-pet","immuno-pet"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"urological","burden":"GLOBOCAN 2022 estimated 614,298 new cases and 220,596 deaths worldwide, about 75% of them in men. The newer GLOBOCAN 2024 release put incidence at 635,264 cases, ranked eighth worldwide with an age-standardised rate of 5.5 per 100,000, and mortality at 227,626 deaths, ranked thirteenth at 1.8 per 100,000. SEER projects 84,530 new US cases and 17,870 US deaths for 2026, with an incidence rate of 17.9 and a death rate of 4.1 per 100,000.","subtypes":["Non-muscle-invasive bladder cancer (Ta, Tis/carcinoma in situ, T1)","Muscle-invasive bladder cancer","Metastatic urothelial carcinoma","FGFR2/3-altered urothelial carcinoma"],"biomarkers":["FGFR3/FGFR2 genetic alterations, present in about 20% of metastatic urothelial carcinoma and required by an FDA-approved companion diagnostic to qualify patients for erdafitinib","PD-L1 expression, used as a stratification factor in the CheckMate 274 adjuvant nivolumab trial though not required for pembrolizumab use in NMIBC","Urine cytology and cystoscopy with biopsy, used to define complete response in BCG-unresponsive-disease trials"],"standardOfCare":[{"setting":"Non-muscle-invasive disease (Ta/Tis/T1)","approach":"Transurethral resection of the bladder tumour followed by a single immediate instillation of intravesical chemotherapy, typically mitomycin, with periodic intravesical BCG instillations for higher-risk disease based on risk stratification.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq"}},{"setting":"NMIBC, BCG-unresponsive","approach":"Pembrolizumab or intravesical nadofaragene firadenovec gene therapy for patients ineligible for or declining cystectomy, with radical cystectomy remaining the definitive option for those medically fit for it.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq"}},{"setting":"Muscle-invasive disease","approach":"Neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy and urinary diversion, or bladder-sparing trimodal chemoradiation; perioperative pembrolizumab with enfortumab vedotin around cystectomy for cisplatin-ineligible and, since 2026, cisplatin-eligible patients; adjuvant nivolumab after cystectomy for those at high recurrence risk.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq"}},{"setting":"Metastatic disease, first line","approach":"Enfortumab vedotin plus pembrolizumab for all patients regardless of cisplatin eligibility; platinum-based chemotherapy where the combination is unavailable; erdafitinib after progression in patients with a susceptible FGFR3 alteration.","refs":[],"guideline":{"url":"https://www.cancer.gov/types/bladder/hp/bladder-treatment-pdq"}}],"stateOfArt":["Enfortumab vedotin, a Nectin-4-directed antibody-drug conjugate, combined with pembrolizumab has replaced platinum chemotherapy as first-line therapy for locally advanced or metastatic urothelial cancer, with the EV-302/KEYNOTE-A39 trial reporting median overall survival of 31.5 months against 16.1 months for chemotherapy.","Perioperative use of pembrolizumab with enfortumab vedotin around radical cystectomy was approved in 2025 for cisplatin-ineligible muscle-invasive disease and extended in 2026 to cisplatin-eligible patients, based on KEYNOTE-B15/EV-304, which reported a 47% reduction in the risk of event-free survival events compared with neoadjuvant chemotherapy and surgery.","Guideline bodies disagree on the role of PET in staging: AUA, EAU and NCCN restrict FDG PET/CT to selected or indeterminate cases in initial staging, while ESMO and EAU jointly recommend it specifically for staging oligometastatic patients being considered for radical treatment, reflecting a genuine transatlantic practice discrepancy."],"history":[{"year":2020,"title":"FDA approved pembrolizumab for BCG-unresponsive, high-risk non-muscle-invasive bladder cancer with carcinoma in situ","note":"Approved 8 January 2020 for patients ineligible for or declining cystectomy.","refs":[]},{"year":2021,"title":"Nivolumab approved for adjuvant treatment of high-risk urothelial carcinoma after radical resection","note":"Based on CheckMate 274, median disease-free survival 20.8 versus 10.8 months; approved 19-20 August 2021.","refs":[]},{"year":2022,"title":"Nadofaragene firadenovec-vncg (Adstiladrin) approved","note":"First gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ, approved 16 December 2022.","refs":[]},{"year":2023,"title":"Enfortumab vedotin plus pembrolizumab granted full FDA approval for all locally advanced or metastatic urothelial cancer regardless of cisplatin eligibility","note":"Based on EV-302/KEYNOTE-A39, median overall survival 31.5 versus 16.1 months; approved 15 December 2023.","refs":[]},{"year":2024,"title":"Erdafitinib converted to full FDA approval for FGFR3-altered metastatic urothelial carcinoma","note":"For patients who progressed on at least one prior systemic therapy, approved 19 January 2024.","refs":[]},{"year":2025,"title":"Perioperative pembrolizumab plus enfortumab vedotin approved for cisplatin-ineligible muscle-invasive bladder cancer","note":"Based on KEYNOTE-905/EV-303; approved 21 November 2025.","refs":[]},{"year":2026,"title":"Perioperative pembrolizumab plus enfortumab vedotin indication expanded to cisplatin-eligible muscle-invasive bladder cancer","note":"Based on KEYNOTE-B15/EV-304 in 808 patients, a 47% reduction in event-free survival events versus neoadjuvant chemotherapy and surgery.","refs":[]}],"pipeline":["opp-nectin4-imaging-urothelial","nectin4","fdg-pet","immuno-pet"],"openProblems":["Nodal staging before radical cystectomy is poor across all imaging modalities, with pooled sensitivity of about 0.40 for CT, 0.60 for MRI and 0.56 for FDG PET/CT despite specificities around 0.91 to 0.92, meaning occult nodal metastases are commonly missed pre-operatively.","FDG PET/CT's value in the pelvis is intrinsically limited by physiological urinary excretion of the tracer, which obscures the primary tumour bed and adjacent nodes in exactly the region that matters most for surgical planning.","No international guideline consensus exists on the routine role of PET in initial staging, with US-oriented societies restricting its use and European societies recommending it for oligometastatic staging.","Only about 20% of metastatic urothelial carcinoma patients carry an FGFR2/3 alteration actionable with erdafitinib, leaving most patients without a validated targeted-therapy biomarker pathway after platinum and immunotherapy failure.","Distant disease still carries a five-year relative survival of only 9.6% despite recent enfortumab vedotin plus pembrolizumab and adjuvant immunotherapy advances, showing these regimens extend but do not yet cure metastatic disease for most patients."],"prognosis":{"text":"Survival depends strongly on stage at diagnosis. SEER reports five-year relative survival of 79.1% overall for patients diagnosed between 2016 and 2022: 98.0% for in situ disease, which is half of all cases, 73.0% for localised disease at 34% of cases, 41.8% for regional disease at 7% of cases, 9.6% for distant disease at 6% of cases, and 50.8% for unknown or unstaged disease at 3% of cases. These are population averages and do not predict any individual patient's outcome.","sources":[{"label":"SEER Cancer Stat Facts: bladder cancer","url":"https://seer.cancer.gov/statfacts/html/urinb.html"}]}},"route":"/indications/urothelial-cancer/","neighbours":{"target":[{"id":"nectin4","kind":"target","name":"Nectin-4","route":"/targets/nectin4/"}],"technology":[{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"immuno-pet","kind":"technology","name":"Immuno-PET","route":"/technologies/immuno-pet/"}],"opportunity":[{"id":"opp-nectin4-imaging-urothelial","kind":"opportunity","name":"A liver-cleared Nectin-4 tracer for urothelial cancer","route":"/opportunities/opp-nectin4-imaging-urothelial/"}]}}